Abstract
Abstract In the gut, the interaction between the tumor tissue and its microenvironment including the microbiota and immune cells may play a significant role in the carcinogenic process. Here we studied whether the anti-carcinogenic effects of berry diets were mediated by changes in the gut microbiota and immune cells. Male and female Min mice were fed modified high-fat AIN93-G diets containing 10% (w/w) freeze-dried bilberry or cloudberry for 10 weeks. The control diet was similar but without any berries. Mucosal B and T lymphocytes were analysed using immunohistochemical staining. The microbial profile was determined carrying out PCR-DGGE analysis using bacterial genomic DNA extracted from caecal contents. Microbial PCR-DGGE profiles contained 10-19 amplicons, indicating that the microbiota in the mouse cecum contents is diverse. According to their PCR-DGGE patterns, samples of control and cloudberry-fed mice could be divided to well-defined subgroups both visually and using Molecular Analyst software. Instead, visual grouping of the samples of bilberry-fed mice was impossible and the samples were only grouped using the software. In the control mice, amplicons a-d were present in all samples but on the basis of their intensity, amplicons b-d represented the dominant species. In the cloudberry mice, amplicons a, c, d, e and f existed in all samples but some of them lacked a pronounced amplicon b. In the bilberry mice, the amplicons a-e existed in all samples. In addition, bilberry samples contained amplicon g that seemed to be more prevalent and intense than in the samples of the other two groups. The amplicon g was sequenced and found to belong to the Clostridiales order of the Clostridia class in the Firmicutes phylum and to represent an uncultured bacterium clone abc21b07.x1: AY667976. Cloudberry feeding resulted in a smaller density of mucosal CD3+ T lymphocytes (p=0.149) and a significantly smaller ratio of intraepithelial to total CD3+ T lymphocytes (p=0.034) when compared to the control group. Furthermore, there was a significant positive correlation (p=0.012) between the ratio of intraepithelial to total CD3+ T lymphocytes and adenoma burden in the small intestine of Min mice. Interestingly, no difference in the density of any lymphocytes was found between the bilberry and the control group. Berry feeding did not affect the density of B lymphocytes in the intestinal mucosa. Here we show that berry feeding changes the microbiota and the distribution of immune cells in the intestine of Min mice and these changes are associated with adenoma formation. Citation Format: Anne-Maria Pajari, Essi Paivarinta, Johanna Maukonen, Mikael Niku, Anu Heiman-Lindh, Maria Saarela, Marja Mutanen. Berry feeding changes gut microbiota and immune function in association with adenoma formation in the Min mouse. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4871. doi:10.1158/1538-7445.AM2013-4871
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